Meperidine attenuates the secretion but not the transcription of interleukin 1 beta in human mononuclear leukocytes.
BACKGROUND
The infusion of amphotericin-B (AmB) often produces clinically distressing rigors and chills, which promptly abate with intravenous injection of meperidine, although its mechanism of action is unknown.


OBJECTIVE
To examine the effects of meperidine on the transcription or secretion of Interleukin 1 beta (IL-1 beta) in human mononuclear leukocytes (MNL) exposed in vitro to the lipopolysaccharide (LPS) contained in Escherichia coli endotoxin or to AmB.


METHODS
Blood was drawn from eight healthy adult volunteers. The blood was centrifuged, and the layer containing MNL was separated; incubated with various combinations of medium, meperidine, and AmB; then tested for IL-1 content to determine the effect of meperidine on MNL secretion of IL-1 beta. To determine the effect on MNL transcription of IL-1 beta, the RNA was extracted from cells and the IL-1 beta was measured using one of two different methods.


RESULTS
Incubation of human MNL in the presence of LPS or AmB significantly increased transcription of IL-1 beta mRNA and secretion of IL-1 beta. Addition of meperidine to these cultures significantly reduced LPS-induced, but not AmB-induced, secretion of IL-1 beta in vitro. Meperidine did not alter IL-1 beta mRNA levels in MNL exposed to LPS or AmB.


CONCLUSIONS
These data suggest that meperidine decreases rigors and chills in part by decreasing MNL secretion of IL-1 beta through a posttranscriptional mechanism.
McCarthy
D O
DO
School of Nursing, University of Wisconsin-Madison, USA.
Murray
S
S
Galagan
D
D
Gern
J E
JE
Hutson
P R
PR
D000328:Adult; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008614:Meperidine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D009294:Narcotics; D008614:Meperidine